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• W2051295642 abstract "To the Editor: We report on a series of 10 patients who exhibited increased temperature variation before the development of fever in the evolution of sepsis syndrome. This case series serves as an introduction to a concept that we strongly believe to be valid. It is the first report of using temperature pattern to recognize infections in afebrile patients, but we think that it is an area that merits further investigation. Early institution of antimicrobial therapy in patients with sepsis improves survival (1). Fever is a universally accepted marker for infection (2, 3). Although fever may be an early sign of infection, many patients (i.e., malnourished, renal failure, immune suppressed, and the elderly) do not develop fever despite serious life-threatening infections (3). Failure to mount a fever is associated with worse outcome in septic shock (4) and may be a reflection of impaired host immunity or hormonal factors. Some investigators have even suggested that fever may be important for sepsis survival (5). The authors have observed that early infection in the intensive care unit can occasionally be appreciated before the onset of fever by noting subtle changes in body temperature pattern. Based on our prior patients, we hypothesized that changes in patients' baseline temperature patterns could be an early indicator of developing sepsis. This case series identifies 10 patients with documented gram-negative sepsis and characteristic changes in the temperature profile before the clinical recognition of sepsis. Careful evaluation of the patient profiles revealed that changes in the temperature pattern often preceded more obvious signs of infection (including the development of fever) by 1 to 2 days. Several key temperature changes that we have observed to precede a classic fever spike are an increase in the magnitude of the daily fluctuations in body temperature and an increase in oscillatory irregularity (Fig. 1). Although heart rate variability (6) and cardiac output variability (7) have been reported in septic patients, changes in temperature profiles in the afebrile patient has not been previously described as a marker of infection.Fig. 1: A, The normal diurnal temperature curve is 0.7°C. A number of changes in the daily body temperature pattern can be observed before development of fever including (B) a change in amplitude and/or irregularity or (C) an increase in frequency and/or irregularity. The actual observed patient temperature profile may combine features of several of these patterns.This single-center, retrospective analysis identified 10 patients with gram-negative severe sepsis or septic shock hospitalized between January 2002 and February 2008 at a 1,111-bed academic medical center. All patients had gram-negative bacteremia and met criteria for severe sepsis or septic shock by International Classification of Diseases, Ninth Revision criteria, as previously defined by Angus et al. (8). The data set was restricted to gram-negative bacteria because of the presumed similarity in the cause of fever with gram-negative bacteremia (e.g., lipopolysaccharide release). Furthermore, isolated gram-negative bacteremia less likely represents false-positive contamination as may occur with gram-positive organisms. Temperature data were collected from the medical record for the period preceding collection of the blood culture and were analyzed to identify patients with changes in temperature profile consistent with patterns the authors have identified in clinical practice. Fever was defined as temperature greater than or equal to 38.3°C (9) in accordance with the recommendations of the American College of Critical Care Medicine and the Infectious Diseases Society of America, and the site for measuring temperature varied according to customary clinical practice. Temperature profiles were evaluated by at least three authors. The Washington University Human Research Protection Office approved the data collection for this case series and granted waiver of informed consent. During the 6-year period, 281 patients had blood cultures with gram-negative organisms, severe sepsis or septic shock, and 3 days of temperature data before diagnosis. The authors selected 10 temperature profiles that best illustrated characteristic alterations in body temperature before the development of fever or of clinical septic shock. The median time in the hospital before the development of infection was 19.5 days. Compared with the entire patient cohort, the 10 patients with temperature pattern changes did not differ significantly with respect to baseline median modified Acute Physiology And Chronic Health Evaluation II (26 vs. 24, P = 0.58), age (57 vs. 60, P = 0.32), or mortality (60% vs. 41%, P = 0.12). None of the patients in this sample were on dialysis or receiving antipyretics during the recorded temperature profile, and no specific changes were identified in their care at the time of changes in the temperature profile. Figure 2 represents the temperature profiles of the 10 patients who developed changes in their body temperature pattern as an early marker of sepsis. Each patient lost tight homeostatic temperature regulation before the development of fever-typically preceding the identification of fever by 1 to 2 days.Fig. 2: Horizontal axis is days before diagnostic blood culture being drawn (represented by black vertical line); shaded gray box represents fever (temperature 38.3°C); red dotted line represents the first fever; yellow shaded box illustrates the portion of the tracing where infection may have been diagnosed earlier. Note the difference between the preseptic period and the patient's baseline.Early recognition and treatment of serious infection dramatically improve outcome in patients with sepsis (1). However, typical findings suggestive of infection (i.e., increasing white blood cell count, development of fever) may not be present in all patients (10). An inexpensive, simple method that could alert clinicians early to the onset of infection would be beneficial as earlier attention to detecting and treating infection could have a major impact on survival. We theorize that patients with gram-negative sepsis have early clinical release of small amounts of endotoxin. These subclinical quantities start to cause some instability in homeostatic mechanisms before fever or hemodynamic collapse, but are nonetheless detectable on careful physiologic review. If this technique were validated, computerized clinical information systems could warn physicians of suspicious changes in body temperature profile. As these programs become more advanced, they may be able to recognize patterns in real time and prompt physicians to act. Detecting a change in baseline body temperature may not necessarily indicate that a patient has impending sepsis that requires a change of therapy. It should, however, motivate the physician to reevaluate the patient for developing infection. The change in temperature pattern should be interpreted in the context of other evidence of infection. This series is limited by the unknown test characteristics of temperature variability (e.g., sensitivity, specificity). Temperature variability is likely a nonspecific finding (like fever) and could be due to both infectious and noninfectious etiologies (11). Fever pattern has been explored only in febrile patients previously (12), and we think it may provide a unique early warning in afebrile patients. A prospective study should be performed to answer this question. Changes in temperature pattern may be an early sign of infection and can precede or occur in the absence of fever. Prospective analyses should be performed to validate this clinical tool in practice. Nicholas M. Mohr Division of Critical Care Department of Anesthesiology, and Division of Emergency Medicine Washington University School of Medicine St. Louis, Missouri Richard S. Hotchkiss Division of Critical Care Department of Anesthesiology Washington University School of Medicine St. Louis, Missouri Scott T. Micek Department of Pharmacy Barnes-Jewish Hospital St. Louis, Missouri Sulaman Durrani Division of Critical Care Department of Anesthesiology Washington University School of Medicine St. Louis, Missouri Brian M. Fuller Division of Critical Care Department of Anesthesiology, and Division of Emergency Medicine Washington University School of Medicine St. Louis, Missouri" @default.
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• W2051295642 date "2011-09-01" @default.
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• W2051295642 title "Change in Temperature Profile May Precede Fever and be an Early Indicator of Sepsis" @default.
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